Cinnamic acid-GPR109A pathway improves skeletal muscle hypertrophy and metabolism

Cinnamic acid (CA), a phenylalanine metabolite found in various plants, such as Cinnamomi ramulus, a key role in regulating biological process, like proliferation, osteoblast differentiation, glucose and lipid metabolism, angiogenesis, and the activation of brown adipocytes. However, its physiological role in manipulating skeletal muscle phenotype is unclear.

In this study, we summarize its amazing role in skeletal muscle hypertrophy and mitochondrial metabolism and briefly clarify the mechanical function of GPR109A/PKA pathway under those process.

In vivo, C57BL/6 mice were subjected to acute and chronic CA supplement to investigate its function on skeletal muscle development, exercise capacity and systemic metabolism. In vitro, C2C12 cells was used to quantify protein synthesis, mitochondrial biogenesis and intracellular ATP dynamics.

Chronic CA supplementation effectively increased energy expenditure and significantly altered lean fat mass and gut microbiota composition in mice, while acute addition of CA enhanced the tibialis anterior muscle index, tricarboxylic acid cycle activation, and exercise capacity. Mechanically, we demonstrated that CA induces myotube hypertrophy by promoting protein synthesis in vitro. Meanwhile, the mitochondrial content and intracellular ATP level were significantly accumulated through the activation of GPR109A and its downstream PKA/CREB signalling pathway, and which is also could regulated by CA directly binding.

These results firstly reveal the critical role of CA in promoting skeletal muscle hypertrophy and mitochondrial metabolism via the GPR109A/PKA pathway, which shows experimental basic for CA to be a potential food source for improving metabolism. Most importantly form a treatment standpoint, CA could be a newly treatment for sarcopenia.